This project, begun in 1969, examines the pathophysical mechanisms responsible for cyst formation and enlargement in the susceptible mammalian kidney. In earlier years it examined the polycystic and medullary cystic forms of cystic kidney diseases of man for its clinical base. The studies currently in progress utilize a laboratory model of these conditions, the diphenylamine-fed rat. Both cystic and precystic kidneys are being studied. Standard techniques of nephron dissection, and nephron micropuncture are being applied in efforts to identify intratubular conditions which favor cyst formation and enlargement. It is hoped that the results of these studies will suggest approaches to the arrest and/or prevention of cyst formation and therefore renal failure in susceptible humans.